Mechanisms of production of two new microglial growth-differentiation factors from brain astrocytes and neurons

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Thymic myoid cells were found in many vertebrates. In particular, in human these cells are suggested to relate to autoimmune disease myasthenia gravis. We thought that these cells might have important roles in physiology. We succeeded in cloning myoid cells from the rat thymus. Indeed, these cells produce many cytokines, including an 80-kDa and 100-kDa haemopoietic factors. Both of them preferentially induce monocytic lineage cells. Using specific antibodies against these factors, we found that many myoid cells are increased in number and are producing these factors in the hyperplastic thymus associated with myasthenia gravis. Furthermore, we detected that these factors play important roles in specific proliferation of B-cells that recognized myoid cell s-own AChR. Brain also uses cytokines. Some of them are common to those used in the immune system. Expectedly, brain cells including neurons and glial cells produce the two factors. The purified two factors stimulate the growth and differentiation of microglial cells, suggesting that the new factors play important roles in diversification of monocytic lineage cells, together with macrophage colony stimulating factor and granulocyte-macrophage colony stimulating factor. Furthermore, these factors also stimulated MAPK of neurons, suggesting that they play important roles in neuron survival. We also succeeded in producing recombinant 80-kDa and 100-kDa factors.